On June 7, 2023 Immune-Onc Therapeutics, Inc. ("Immune-Onc"), a private, clinical-stage oncology company dedicated to the discovery and development of novel biotherapeutics by targeting inhibitory receptors on myeloid cells, reported Phase 1 data for IO-202, a first-in-class humanized IgG1 monoclonal antibody targeting Leukocyte Immunoglobulin-Like Receptor B4 (LILRB4, also known as ILT3) (Press release, Immune-Onc Therapeutics, JUN 7, 2023, View Source [SID1234632571]). Data from the dose escalation part of the Phase 1 study evaluating patients with relapsed or refractory (R/R) acute myeloid leukemia (AML) and chronic myelomonocytic leukemia (CMML) will be presented during a poster session at the European Hematology Association (EHA) (Free EHA Whitepaper) Annual Meeting in Frankfurt, Germany on June 9, 2023.

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"AML is the most common form of acute leukemia in adults in the U.S. and is characterized by high rates of relapsed and refractory disease. Monocytic AML is especially in need of break-through medicine as it is often resistant to standard-of-care treatment. CMML is a rare leukemia overlap syndrome characterized by the accumulation of monocytes in the blood and bone marrow, with both myeloproliferative and myelodysplastic features," said IO-202 Phase 1 investigator, Courtney DiNardo, M.D., MSCE, associate professor, Department of Leukemia, Division of Cancer Medicine at The University of Texas MD Anderson Cancer Center, Houston, TX. "These results, showing strong safety and promising clinical activity as both monotherapy and in combination with a standard-of-care chemotherapy for monocytic AML and CMML, suggest that LILRB4 may be an important therapeutic target for hard-to-treat blood cancers."

"We are very encouraged with the efficacy data of IO-202 as a single agent and in combination with azacitidine in heavily pre-treated patients with R/R AML and CMML," said Paul Woodard, MD, chief medical officer of Immune-Onc. "Based on the data, we have developed a patient enrichment strategy for the ongoing dose expansion phase of the study to select AML patients who would most likely respond to IO-202. We are also pleased to receive the FDA Fast Track designation for IO-202 for the treatment of R/R CMML, which follows the R/R AML Fast Track designation received in 2022. We look forward to working closely with the FDA and trial investigators to accelerate the clinical development of IO-202 in hematologic malignancies."

The Phase 1 multicenter, open-label, dose escalation study of IO-202 assessed the safety and tolerability of IO-202 in successive cohorts of patients with R/R AML with monocytic differentiation and R/R CMML as its primary objective. Secondary and exploratory objectives included pharmacokinetics, immunogenicity, pharmacodynamic (PD) biomarker effects, and clinical response rate of IO-202 as a monotherapy and in combination with azacitidine (AZA).

Treatment with IO-202 was well tolerated. There were no dose-limiting toxicities observed and a maximum tolerated dose was not reached. In the monotherapy treatment cohorts, one CMML patient demonstrated clinical benefit for more than one year and one AML patient achieved a partial response (PR). In combination therapy cohorts, Complete Remission (CR) has been achieved and is on-going for over 10 months in an AML patient with high LILRB4 expression. Additionally, 3 out of 5 CMML patients achieved clinical benefit including Optimal Marrow Response.

Based on the promising results of the dose escalation part of the study and utilizing a biomarker driven patient selection strategy, the Company has opened dose expansion cohorts to enroll AML patients with monocytic differentiations and high LILRB4, and CMML patients (IO-202-CL-001; NCT04372433).

Poster presentation details are as follows:

Abstract Number: P536
Title: A first-in-human Phase 1 study of IO-202 (anti-LILRB4 mAb) in Acute Myeloid Leukemia (AML) with monocytic differentiations and Chronic Myelomonocytic Leukemia (CMML) patients.
Presenter: Courtney DiNardo, M.D., MSCE, Associate Professor, Department of Leukemia, Division of Cancer Medicine at The University of Texas MD Anderson Cancer Center, Houston, TX
Session Title: Acute myeloid leukemia – Clinical
Session Date and Time: Friday, June 9, 6:00 p.m. – 7:00 p.m. CEST

Abstracts and full session details can be accessed through the EHA (Free EHA Whitepaper) Online Program Planner

ABOUT IO-202

IO-202 is a humanized IgG1 monoclonal antibody (mAb) with high affinity and specificity towards LILRB4 (also known as ILT3). It blocks the interaction of LILRB4 with multiple ligands, including ApoE and Fibronectin, and has broad potential in blood cancers and solid tumors. In hematologic malignancies, preclinical studies showed that IO-202 causes depletion of cells expressing high LILRB4 through antibody-dependent cellular cytotoxicity (ADCC) and antibody-dependent cellular phagocytosis (ADCP), converts a "don’t kill me" to a "kill me" signal by activating T cell killing and converts a "don’t find me" to a "find me" signal by inhibiting infiltration of blood cancer cells. In the context of solid tumors, preclinical data presented at the 2021 American Association for Cancer Research (AACR) (Free AACR Whitepaper) annual meeting demonstrate that IO-202 enhances dendritic cell function and T cell activation in vitro and inhibits tumor growth in an immune competent model in vivo.

IO-202 has two ongoing clinical studies in the U.S.: The Phase 1 trial is currently enrolling expansion cohorts of patients with monocytic (LILRB4 high) acute myeloid leukemia (AML) or chronic myelomonocytic leukemia (CMML) in combination with standard-of-care agents such as azacitidine +/- venetoclax (NCT04372433). The U.S. Food and Drug Administration granted IO-202 Orphan Drug designation for treatment of AML in 2020, as well as Fast Track designations for relapsed or refractory AML in 2022 and relapsed or refractory CMML in 2023. The second Phase 1 trial of IO-202 is currently enrolling patients with advanced solid tumors to evaluate IO-202 as a monotherapy and in combination with an anti-PD-1 (NCT05309187).